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Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming.

ABSTRACT: Macrophages are plastic cells that can switch among different states according to bioenergetic or biosynthetic requirements. Our previous work demonstrated that the transcription factor Forkhead Box Protein 1 (FoxO1) plays a pivotal role in regulating the function of macrophages, but the underlying mechanisms are still unclear. Here we identify FoxO1 as a regulator of macrophage function through metabolic reprogramming. Transcriptomic and proteomic analyses showed that the deficiency of FoxO1 results in an alternatively activated (M2) phenotype of macrophages, with lower expression of inflammatory response- and migration-associated genes. Using the high content screening and analysis technology, we found that deletion of FoxO1 in macrophages slows their migration rate and impairs their function to limit tumor cell growth in vitro. Next, we demonstrated that glycolysis is inhibited in FoxO1-deficient macrophages, which leads to the observed functional changes and the reduced tumor suppression capability. This prospective study shows that FoxO1 serves as a bridge between metabolism and macrophage function.

SUBMITTER: Yan K

PROVIDER: S-EPMC7518254 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming.

Yan Kai K Da Tian-Tian TT Bian Zhen-Hua ZH He Yi Y Liu Meng-Chu MC Liu Qing-Zhi QZ Long Jie J Li Liang L Gao Cai-Yue CY Yang Shu-Han SH Zhao Zhi-Bin ZB Lian Zhe-Xiong ZX

Cell death & disease 20200924 9

Macrophages are plastic cells that can switch among different states according to bioenergetic or biosynthetic requirements. Our previous work demonstrated that the transcription factor Forkhead Box Protein 1 (FoxO1) plays a pivotal role in regulating the function of macrophages, but the underlying mechanisms are still unclear. Here we identify FoxO1 as a regulator of macrophage function through metabolic reprogramming. Transcriptomic and proteomic analyses showed that the deficiency of FoxO1 re ...[more]

PMID: 32973162

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Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming.

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Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming.

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